Time-of-day effects on motor unit firing and muscle contractile properties in humans.

Intrinsic factors related to neuromuscular function are time-of-day dependent, but diurnal rhythms in neural and muscular components of the human neuromuscular system remain unclear. The present study aimed to investigate the time-of-day effects on neural excitability and muscle contractile properties by assessing the firing properties of tracked motor units and electrically evoked twitch muscle contraction. In 15 young adults (22.9 ± 4.7 yr), neuromuscular function was measured in the morning (10:00), at noon (13:30), in the evening (17:00), and at night (20:30). Four measurements were completed within 24 h. The measurements consisted of maximal voluntary contraction (MVC) strength of knee extension, recording of high-density surface electromyography (HDsEMG) from the vastus lateralis during ramp-up contraction to 50% of MVC, and evoked twitch torque of knee extensors by electrical stimulation. Recorded HDsEMG signals were decomposed to individual motor unit firing behaviors and the same motor units were tracked among the times of day, and recruitment thresholds and firing rates were calculated. The number of detected and tracked motor units was 127. Motor unit firing rates significantly increased from morning to noon, evening, and night (P < 0.01), but there were no significant differences in recruitment thresholds among the times of day (P > 0.05). Also, there were no significant effects of time of day on evoked twitch torque (P > 0.05). Changes in the motor unit firing rate and evoked twitch torque were not significantly correlated (P > 0.05). These findings suggest that neural excitability may be affected by the time of day, but it did not accompany changes in peripheral contractile properties in a diurnal manner.NEW & NOTEWORTHY We investigated the variations of tracked motor unit firing properties and electrically evoked twitch contraction during the day within 24 h. The variation of motor unit firing rate was observed, and tracked motor unit firing rate increased at noon, in the evening, and at night compared with that in the morning. The variation in motor unit firing rate was independent of changes in twitch contraction. Motor unit firing rate may be affected by diurnal rhythms.

Impact of maternal obesity on resting muscle sympathetic nerve activity during uncomplicated pregnancy: a longitudinal assessment.

Maternal obesity increases the risk of adverse pregnancy outcomes. The mechanisms that contribute to this elevated risk are unclear but may be related to greater activity of the sympathetic nervous system, which is associated with hypertensive disorders of pregnancy. We hypothesized that resting muscle sympathetic nerve activity (MSNA) would be greater in women with obesity during pregnancy when compared with normal-weight women. Blood pressure, heart rate, and MSNA were recorded during 5 min of supine rest in 14 normal-weight women [body mass index (BMI) 22.1 ± 2.1 (SD) kg/m2] and 14 women with obesity (BMI 33.9 ± 3.5 kg/m2) during (early and late) pregnancy and postpartum. All women had uncomplicated pregnancies. Resting MSNA burst frequency was not different between groups during early (normal weight 17 ± 10 vs. obesity 22 ± 15 bursts/min, P = 0.35) but was significantly greater in the obesity group during late pregnancy (23 ± 13 vs. 35 ± 15 bursts/min, P = 0.031) and not different postpartum (10 ± 6 vs. 9 ± 7 bursts/min, P = 0.74). These findings were also apparent when comparing burst incidence and total activity. Although still within the normotensive range, systolic blood pressure was greater in the obesity group across all time points (P = 0.002). Diastolic blood pressure was lower during pregnancy compared with postpartum (P < 0.001) and not different between groups (P = 0.488). Heart rate increased throughout pregnancy in both groups (P < 0.001). Our findings suggest that maternal obesity is associated with greater increases in sympathetic activity even during uncomplicated pregnancy. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.NEW & NOTEWORTHY The impact of maternal obesity on resting muscle sympathetic nerve activity was examined during (early and late) and after uncomplicated pregnancy. Resting muscle sympathetic nerve activity is not different during early pregnancy or postpartum but is significantly elevated in women with obesity during late pregnancy when compared with normal-weight women. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.

Subtetanic neuromuscular electrical stimulation can maintain Wingate test performance but augment blood lactate accumulation.

PURPOSE: Concentration- and time-dependent effect of lactate on physiological adaptation (i.e., glycolytic adaptation and mitochondrial biogenesis) have been reported. Subtetanic neuromuscular electrical stimulation (NMES) with voluntary exercise (VOLES) can increase blood lactate accumulation. However, whether this is also true that VOLES can enhance the blood lactate accumulation during sprint exercise is unknown. Thus, we investigated whether VOLES before the Wingate test can enhance blood lactate accumulation without compromising Wingate exercise performance. METHODS: Fifteen healthy young males (mean [SD], age: 23 [4] years, body mass index: 22.0 [2.1] kg/m2) volunteered. After resting measurement, participants performed a 3-min intervention: VOLES (NMES with free-weight cycling) or voluntary cycling alone, which matched exercise intensity with VOLES (VOL, 43.6 [8.0] watt). Then, they performed the Wingate test with 30 min free-weight cycling recovery. The blood lactate concentration ([La]b) was assessed at the end of resting and intervention, and recovery at 1, 3, 5, 10, 20, and 30 min. RESULTS: [La]b during intervention was higher with VOLES than VOL (P = 0.011). The increase in [La]b after the Wingate test was maintained for longer with VOLES than VOL at 10- and 20-min recovery (P = 0.014 and 0.023, respectively). Based on the Wingate test, peak power, mean power, and the rate of decline were not significantly different between VOLES and VOL (P = 0.184, 0.201, and 0.483, respectively). CONCLUSION: The combination of subtetanic NMES with voluntary exercise before the Wingate test has the potential to enhance blood lactate accumulation. Importantly, this combined approach does not compromise Wingate exercise performance compared to voluntary exercise alone.

Association between physical fitness tests and neuromuscular properties.

PURPOSE: While various fitness tests have been developed to assess physical performances, it is unclear how these tests are affected by differences, such as, in morphological and neural factors. This study was aimed to investigate associations between individual differences in physical fitness tests and neuromuscular properties. METHODS: One hundred and thirty-three young adults participated in various general physical fitness tests and neuromuscular measurements. The appendicular skeletal muscle mass (ASM) was estimated by bioelectrical impedance analysis. Echo intensity (EI) was evaluated from the vastus lateralis. During submaximal knee extension force, high-density surface electromyography of the vastus lateralis was recorded and individual motor unit firings were detected. Y-intercept (i-MU) and slope (s-MU) from the regression line between the recruitment threshold and motor unit firing rate were calculated. RESULTS: Stepwise multiple regression analyses revealed that knee extension strength could be explained (adjusted R2 = 0.712) by ASM (ß = 0.723), i-MU (0.317), EI (- 0.177), and s-MU (0.210). Five-sec stepping could be explained by ASM (adjusted R2 = 0.212). Grip strength, side-stepping, and standing broad jump could be explained by ASM and echo intensity (adjusted R2 = 0.686, 0.354, and 0.627, respectively). Squat jump could be explained by EI (adjusted R2 = 0.640). Counter-movement jump could be explained by EI and s-MU (adjusted R2 = 0.631). On the other hand, i-MU and s-MU could be explained by five-sec stepping and counter-movement jump, respectively, but the coefficients of determination were low (adjusted R2 = 0.100 and 0.045). CONCLUSION: Generally developed physical fitness tests were mainly explained by morphological factors, but were weakly affected by neural factors involved in performance.

Can Neuromuscular Electrical Stimulation Enhance the Effect of Sprint Interval Training?

The aim of this study was to determine the effects of subtetanic neuromuscular electrical stimulation combined with voluntary exercise between repeated Wingate tests on sprint exercise performance and blood lactate accumulation during sprint interval training. Fifteen healthy young males volunteered. After 1-min baseline, participants underwent the Wingate test twice. They performed a 4-min intervention between tests: neuromuscular electrical stimulation with free-weight cycling or voluntary cycling alone [43.6 (8.0) watts], which matched oxygen consumption with neuromuscular electrical stimulation with free-weight cycling. The blood lactate concentration was assessed at the end of the baseline, at 3-min intervention, and on recovery at 1, 3, 5, and 10 min after the second Wingate test. Peak and mean blood lactate concentration during recovery were significantly greater with neuromuscular electrical stimulation with free-weight cycling than voluntary cycling alone (P>0.036 and P=0.011, respectively). Peak power, mean power, and rate of decline (fatigue index) were not significantly different between conditions in both Wingate tests (condition/interaction all P>0.300, partial η2<0.1). Subtetanic neuromuscular electrical stimulation combined with voluntary exercise indicated similar exercise performance and fatigue levels during Wingate tests, but enhanced blood lactate accumulation compared to oxygen consumption-matched voluntary cycling during sprint interval training.

Motor Unit Firing Properties During Force Control Task and Associations With Neurological Tests in Children.

The present study aimed to clarify the development of motor unit (MU) firing properties and the association between those neural properties and force steadiness (FS)/neurological tests in 6- to 12-year-old children. Fifty-eight school-aged children performed maximal voluntary knee extension contraction, a submaximal FS test at 10% of maximal voluntary knee extension contraction, knee extension reaction time to light stimulus test, and single-leg standing test, and data from 38 children who passed the criteria were subject to analysis. During the FS test, high-density surface electromyography was recorded from the vastus lateralis muscle to identify individual MU firing activity. FS was improved with an increase in age (r = -.540, P < .001). The MU firing rate (MUFR) was significantly decreased with an increase in age (r = -.343, P = .035). MUFR variability was not associated with age. Although there was no significant correlation between FS and MUFR, FS was significantly correlated with MUFR variability even after adjustment for the effect of age (r = .551, P = .002). Neither the reaction time nor the single-leg standing test was correlated with any MU firing properties. These findings suggest that MUFR variability makes an important contribution to precise force control in children but does not naturally develop with age.

The interactive effects of age and sex on the neuro-cardiovascular responses during fatiguing rhythmic handgrip exercise.

The impact of age on exercise pressor responses is equivocal, likely because of sex-specific neuro-cardiovascular changes with age. However, assessments of the interactive effects of age and sex on muscle sympathetic nerve activity (MSNA) responses to exercise are lacking. We tested the hypothesis that older females would exhibit exaggerated increases in blood pressure (BP) and MSNA discharge patterns during handgrip exercise compared with similarly aged males and young adults. Twenty-five young (25 (2) years; mean (SD)) males (YM; n = 12) and females (YF; n = 13) and 23 older (71 (5) years) males (OM; n = 11) and females (OF; n = 12) underwent assessments of BP, total peripheral resistance (TPR; Modelflow) and MSNA action potential (AP) discharge patterns (microneurography) during incremental rhythmic handgrip exercise and post-exercise circulatory occlusion (PECO). OM demonstrated larger ∆BP and ∆TPR from baseline than YM (both P < 0.001) despite smaller increases in ∆APs/burst (OM: 0.4 (3) vs. YM: 5 (3) spikes/burst, P < 0.001) and ∆AP clusters/burst (OM: 0.1 (1) vs. YM: 1.8 (1) clusters/burst, P < 0.001) during exercise. Testosterone was lower in OM than YM (P < 0.001) and was inversely related to ∆BP but positively related to ∆AP clusters/burst in males (both P = 0.03). Conversely, YF and OF demonstrated similar ∆BP and ∆AP discharge during exercise (range: P = 0.75-0.96). Age and sex did not impact haemodynamics or AP discharge during PECO (range: P = 0.08-0.94). Altogether, age-related changes in neuro-cardiovascular reactivity exist in males but not females during fatiguing exercise and seem to be related to testosterone. This sex-specific impact of age underscores the importance of considering biological sex when assessing age-related changes in neuro-cardiovascular control during exercise. KEY POINTS: Older males have the largest increase in blood pressure despite having the smallest increases in sympathetic vasomotor outflow during rhythmic handgrip exercise. Young males demonstrate greater increases in sympathetic action potential (AP) discharge compared with young females during rhythmic handgrip exercise. Older adults (regardless of sex) demonstrate smaller increases in muscle sympathetic nerve activity (MSNA) burst amplitude and total AP clusters compared with young adults during exercise, as well as smaller increases in integrated MSNA burst frequency, incidence and total MSNA activity during post-exercise circulatory occlusion (i.e. independent effect of age). Males, but not females (regardless of age), reflexively modify AP conduction velocity during exercise. Our results indicate that age and sex independently and interactively impact the neural and cardiovascular homeostatic adjustments to fatiguing small muscle mass exercise.

Age- and sex-related differences in sympathetic vascular transduction and neurohemodynamic balance in humans.

Bursts of muscle sympathetic nerve activity (MSNA) and the ensuing vasoconstriction are pivotal determinants of beat-by-beat blood pressure regulation. Although age and sex impact blood pressure regulation, how these factors affect the central and peripheral arcs of the baroreflex remains unclear. In 27 young [25 (SD 3) yr] males (YM; n = 14) and females (YF; n = 13) and 23 older [71 (SD 5) yr] males (OM; n = 11) and females (OF; n = 12), femoral artery blood flow, blood pressure, and MSNA were recorded for 10 min of supine rest. Sympathetic baroreflex sensitivity (i.e., central arc) was quantified as the relationship between diastolic blood pressure and MSNA burst incidence. Signal averaging was used to determine sympathetic vascular transduction into leg vascular conductance (LVC) for 12 cardiac cycles following MSNA bursts (i.e., peripheral arc). Older adults demonstrated attenuated sympathetic transduction into LVC (both P < 0.001) following MSNA bursts, and smaller increases in sympathetic transduction as a function of MSNA burst size and firing pattern compared with young adults (range, P = 0.004-0.032). YM (r2 = 0.36; P = 0.032) and OM (r2 = 0.51; P = 0.014) exhibited an inverse relationship between the central and peripheral arcs of the baroreflex, whereas females did not (YF, r2 = 0.03, P = 0.621; OF, r2 = 0.06, P = 0.445). MSNA burst incidence was inversely related to sympathetic transduction in YM and OF (range, P = 0.03-0.046) but not in YF or OM (range, P = 0.360-0.603). These data indicate that age is associated with attenuated sympathetic vascular transduction, whereas age- and sex-specific changes are present in the relationship between the central and peripheral arcs of the baroreflex regulation of blood pressure.NEW & NOTEWORTHY Sympathetic vascular transduction is attenuated in older compared with young adults, regardless of biological sex. Males, but not females (regardless of age), demonstrate an inverse relationship between central (sympathetic baroreflex sensitivity) and peripheral (sympathetic vascular transduction) components of the baroreflex arc. Young males and older females exhibit an inverse relationship between resting sympathetic outflow and sympathetic vascular transduction. Our results indicate that age and sex exert independent and interactive effects on sympathetic vascular transduction and sympathetic neurohemodynamic balance in humans.

Longitudinal development of muscle strength and relationship with motor unit activity and muscle morphological characteristics in youth athletes.

Neural and morphological adaptations determine gains of muscle strength. For youth athletes, the importance of morphological adaptation is typically highlighted based on the change in maturity status. However, the long-term development of neural components in youth athletes remains unclear. The present study investigated the longitudinal development of muscle strength, muscle thickness (MT), and motor unit firing activity of the knee extensor and their relationships in youth athletes. Seventy male youth soccer players (mean ± SD age = 16.3 ± 0.6 years) performed neuromuscular, maximal voluntary isometric contraction (MVC), and submaximal ramp contraction (at 30 and 50% MVC) tests with knee extensors, two times with a 10-month measurement interval. High-density surface electromyography was recorded from the vastus lateralis and decomposed to identify each individual motor unit activity. MT was evaluated by the sum of the vastus lateralis and vastus intermedius thicknesses. Finally, sixty-four participants were employed to compare MVC and MT, and 26 participants were employed to analyze motor unit activity. MVC and MT were increased from pre to post (p < 0.05, 6.9 and 1.7% for MVC and MT, respectively). Y-intercept of the regression line between median firing rate vs. recruitment threshold was also increased (p < 0.05, 13.3%). Multiple regression analysis demonstrated that the gains of both MT and Y-intercept were explanatory variables for the gain of strength. These findings suggest that the neural adaptation could also make the important contribution to the strength gain for the youth athletes over a 10-month training period.

Effects of posture changes on dynamic cerebral autoregulation during early pregnancy in women with obesity and/or sleep apnea.

The incidence of syncope during orthostasis increases in early human pregnancy, which may be associated with cerebral blood flow (CBF) dysregulation in the upright posture. In addition, obesity and/or sleep apnea per se may influence CBF regulation due to their detrimental impacts on cerebrovascular function. However, it is unknown whether early pregnant women with obesity and/or sleep apnea could have impaired CBF regulation in the supine position and whether this impairment would be further exacerbated in the upright posture. Dynamic cerebral autoregulation (CA) was evaluated using transfer function analysis in 33 women during early pregnancy (13 with obesity, 8 with sleep apnea, 12 with normal weight) and 15 age-matched nonpregnant women during supine rest. Pregnant women also underwent a graded head-up tilt (30° and 60° for 6 min each). We found that pregnant women with obesity or sleep apnea had a higher transfer function low-frequency gain compared with nonpregnant women in the supine position (P = 0.026 and 0.009, respectively) but not normal-weight pregnant women (P = 0.945). Conversely, the transfer function low-frequency phase in all pregnancy groups decreased during head-up tilt (P = 0.001), but the phase was not different among pregnant groups (P = 0.180). These results suggest that both obesity and sleep apnea may have a detrimental effect on dynamic CA in the supine position during early pregnancy. CBF may be more vulnerable to spontaneous blood pressure fluctuations in early pregnant women during orthostatic stress compared with supine rest due to less efficient dynamic CA, regardless of obesity and/or sleep apnea.

Impaired sympathetic neural recruitment during exercise pressor reflex activation in women with post-traumatic stress disorder.

Muscle sympathetic nerve activity (MSNA) increases during isometric exercise via increased firing of low-threshold action potentials (AP), recruitment of larger, higher-threshold APs, and synaptic delay modifications. Recent work found that women with post-traumatic stress disorder (PTSD) demonstrate exaggerated early-onset MSNA responses to exercise; however, it is unclear how PTSD affects AP recruitment patterns during fatiguing exercise. We hypothesized that women with PTSD (n = 11, 43 [11] [SD] years) would exhibit exaggerated sympathetic neural recruitment compared to women without PTSD (controls; n = 13, 40 [8] years). MSNA and AP discharge patterns (via microneurography and a continuous wavelet transform) were measured during 1 min of baseline, isometric handgrip exercise (IHG) to fatigue, 2 min of post-exercise circulatory occlusion (PECO), and 3 min of recovery. Women with PTSD were unable to increase AP content per burst compared to controls throughout IHG and PECO (main effect of group: P = 0.026). Furthermore, relative to controls, women with PTSD recruited fewer AP clusters per burst during the first (controls: ∆1.3 [1.2] vs. PTSD: ∆-0.2 [0.8]; P = 0.016) and second minute (controls: ∆1.2 [1.1] vs. PTSD: ∆-0.1 [0.8]; P = 0.022) of PECO, and fewer subpopulations of larger, previously silent axons during the first (controls: ∆5 [4] vs. PTSD: ∆1 [2]; P = 0.020) and second minute (controls: ∆4 [2] vs. PTSD: ∆1 [2]; P = 0.021) of PECO. Conversely, PTSD did not modify the AP cluster size-latency relationship during baseline, the end of IHG, or PECO (all P = 0.658-0.745). Collectively, these data indicate that women with PTSD demonstrate inherent impairments in the fundamental neural coding patterns elicited by the sympathetic nervous system during IHG and exercise pressor reflex activation.

Posture-related changes in sympathetic baroreflex sensitivity during normal pregnancy.

Normal pregnancy is associated with vast adjustments in cardiovascular autonomic control. Sympathetic baroreflex sensitivity has been reported to be attenuated during pregnancy in animal models, but most studies in humans are cross-sectional and findings from longitudinal case studies are inconclusive. It remains unclear how sympathetic baroreflex sensitivity is altered longitudinally during pregnancy within an individual in different body postures. Therefore, this study examined the impact of posture on sympathetic baroreflex sensitivity in 24 normal-weight normotensive pregnant women. Spontaneous sympathetic baroreflex sensitivity was assessed during early (6-11 weeks) and late (32-36 weeks) pregnancy and 6-10 weeks postpartum in the supine posture and graded head-up tilt (30° and 60°). In addition, data from the postpartum period were compared with (and no different to) 18 age-matched non-pregnant women to confirm that the postpartum period was reflective of a non-pregnant condition (online supplement). When compared with postpartum (-3.8 ± 0.4 bursts/100 heartbeats/mmHg), supine sympathetic baroreflex sensitivity was augmented during early pregnancy (-5.9 ± 0.4 bursts/100 heartbeats/mmHg, P < 0.001). However, sympathetic baroreflex sensitivity at 30° or 60° head-up tilt was not different between any phase of gestation (P > 0.05). When compared to supine, sympathetic baroreflex sensitivity at 60° head-up tilt was significantly blunted during early (Δ2.0 ± 0.7 bursts/100 heartbeats/mmHg, P = 0.024) and late (Δ1.5 ± 0.6 bursts/100 heartbeats/mmHg, P = 0.049) pregnancy but did not change postpartum (Δ0.4 ± 0.6 bursts/100 heartbeats/mmHg, P = 1.0). These data show that time-course changes in sympathetic baroreflex sensitivity are dependent on the posture it is examined in and provides a foundation of normal blood pressure regulation during pregnancy for future studies in women at risk for adverse pregnancy outcomes.

Effects of salt intake on sympathetic neural and pressor responses to cold pressor test in premenopausal women with a history of normal pregnancy.

Excessive salt intake is considered a risk factor for the development of hypertension. Additionally, aberrant neurocirculatory responses to a cold stimulus are associated with an increased risk of hypertension. This study aimed to determine whether salt loading versus salt reduction would impact hemodynamic and sympathetic neural responses during the cold pressor test (CPT) in premenopausal women with a history of normal pregnancy. Nine healthy premenopausal women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (HS; 250 mEq sodium/day) or low-salt (LS; 50 mEq sodium/day) diet for 1-wk each (∼2 mo apart with the order randomized), while water intake was ad libitum. Laboratory testing was performed following each HS and LS period in the mid-luteal phase of the menstrual cycle. Subjects were in the supine position and beat-by-beat blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were continuously measured during 1-min baseline followed by 2-min CPT, and 3-min recovery. BP and HR increased during the CPT (both P < 0.001); the responses were similar between HS and LS. MSNA increased during the CPT, but the increment (Δ) was greater during HS than LS (29 ± 6 vs. 15 ± 4 bursts/min; P < 0.001). The transduction of MSNA for vasoconstriction during the CPT was lower in HS (P < 0.05). Thus, salt loading augments sympathetic neural reactivity to the cold stimulus with similar pressor responses compared with salt reduction, which may be attributed to the blunted neurovascular transduction-a compensatory mechanism for hemodynamic homeostasis in premenopausal women with a history of normal pregnancy.

Impact of high-salt versus low-salt intake on the response of sympathetic baroreflex sensitivity to orthostasis in women with a history of normal pregnancy.

Previous studies have demonstrated that sympathetic baroreflex sensitivity (BRS) increases during orthostatic stress in humans. We recently showed that dietary salt intake affects sympathetic neural control in healthy premenopausal women. This study aimed to determine whether salt loading versus salt reduction would impact sympathetic BRS during orthostasis in premenopausal women with a history of normal pregnancy. Nine healthy women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (250 mEq sodium/day) or low-salt (50 mEq sodium/day) diet for 1 wk each (∼2 mo apart with the order randomized), whereas water intake was ad libitum. Laboratory testing was performed following each high- and low-salt period in the midluteal phase of the menstrual cycle. Hemodynamics and muscle sympathetic nerve activity (MSNA) were measured at baseline (supine; 2 min) and during a graded head-up tilt (30° for 5 min and 60° for 20 min). Sympathetic BRS was assessed during baseline and head-up tilt. Hemodynamics were not different between salt conditions during baseline or tilt. Both supine and upright MSNA indices were lower in high salt than low salt (all P < 0.05), however, there was no interaction effect (P = 0.507-0.996). On moving from supine to upright, sympathetic BRS remained unchanged in high salt but increased in low salt (P = 0.028 for interaction). Thus, salt loading diminishes the responsiveness of sympathetic BRS during orthostasis compared with salt reduction in healthy premenopausal women with prior normal pregnancy. Whether this is one underlying mechanism for salt-induced development of hypertension during ambulation remains to be determined.

Salt intake impacts sympathetic neural control but not morning blood pressure surge in premenopausal women with a history of normal pregnancy.

Salt intake may alter blood pressure (BP) regulation, but no study has investigated the impact of salt reduction versus salt loading on morning blood pressure surge (MBPS) and sympathetic neural control in premenopausal women with a history of normal pregnancy. Nine healthy women (42 ± 3 yr; mean ± SD) were given a low-salt diet (LS; 50 mEq sodium/day) and high-salt diet (HS; 250 mEq sodium/day) for 1 wk each (~2 mo apart with the order randomized), while water intake was ad libitum. Ambulatory BP at 24 h was measured, and the percent change in blood volume (BV) was calculated following LS and HS. MBPS was defined as the morning systolic BP (averaged for 2 h after wake-up) minus the lowest nocturnal systolic BP. Beat-by-beat BP, heart rate, and muscle sympathetic nerve activity (MSNA) were measured during supine rest. Signal averaging was used to characterize changes in beat-by-beat mean arterial pressure and total vascular conductance following spontaneous MSNA bursts to assess sympathetic vascular transduction. Ambulatory BP and MBPS (32 ± 7 vs. 26 ± 12 mmHg, P = 0.208) did not differ between LS and HS. From LS to HS, BV increased by 4.3 ± 3.7% (P = 0.008). MSNA (30 ± 20 vs. 18 ± 13 bursts/100 heartbeats, P = 0.005) was higher, whereas sympathetic vascular transduction was lower in LS than HS (both, P < 0.01). Changes in MSNA from LS to HS were correlated to percent changes in BV (r = -0.673; P = 0.047). Thus, salt intake affects sympathetic neural control but not MBPS in premenopausal women with a history of normal pregnancy. The underlying mechanisms remain unknown; however, alterations in sympathetic vascular transduction may, in part, contribute.NEW & NOTEWORTHY This is the first study to demonstrate that MBPS and ambulatory BP were not affected by salt intake despite a significant change in sympathetic outflow in healthy premenopausal women with a history of normal pregnancy. This may be due to compensatory adaptations in MSNA and sympathetic vascular transduction during salt reduction versus salt loading.

Asymmetric synthesis of (S)-α-(octyl)glycine via alkylation of Ni(II) complex of chiral glycine Schiff base.

Over last decade, the use of Ni(II) complexes, derived from of glycine Schiff bases with chiral tridentate ligands, has emerge as a leading methodology for preparation of structurally diverse Tailor-Made Amino Acids, the key structural units in modern medicinal chemistry, and drug design. Here, we report asymmetric synthesis of derivatives of (S)-α-(octyl)glycine ((S)-2-aminodecanoic acid) and its N-Fmoc derivative via alkylation of chiral nucleophilic glycine equivalent with n-octyl bromide. Under the optimized conditions, the alkylation proceeds with excellent yield (98.1%) and diastereoselectivity (98.8% de). The observed stereochemical outcome and convenient reaction conditions bode well for application of this method for large-scale asymmetric synthesis of (S)-2-aminodecanoic acid and its derivatives.

The effects of aging on the distribution of cerebral blood flow with postural changes and mild hyperthermia.

PURPOSE: Cerebral blood flow (CBF) would be impaired with dual stresses of heat and orthostatic changes, even if those stresses are mild, in the elderly with declined cardio- and cerebrovascular functions with aging. To test the hypothesis, we compared the response of blood flow in the internal carotid artery (ICA) and vertebral artery (VA) to dual stresses of heat and orthostatic changes between the elderly and young individuals. METHODS: Nine elderly and eight young healthy men (71.3 ± 3.0 and 23.3 ± 3.1 years, mean ± SD, respectively) underwent measurements of blood flow in the ICA, VA and external carotid artery (ECA) via ultrasonography. The measurements were obtained in sitting and supine positions under normothermic (NT) and mildly hyperthermic (HT) conditions (ambient temperature 28 °C). Esophageal temperatures increased from NT (36.4 ± 0.2 °C, mean ± SE) to HT (37.4 ± 0.2 °C) with lower legs immersion in 42 °C water. RESULTS: With heat stress, ECA blood flow increased in both postures in both age groups (effect of heat, p < 0.001), whereas ICA blood flow remained unchanged. With postural changes from supine to sitting, ECA blood flow remained unchanged whereas ICA blood flow decreased (effect of posture, p = 0.027) by 18% in NT in the young and by 20% in HT in the elderly. VA blood flow remained unchanged under both heat stress and postural changes. CONCLUSIONS: The CBF is impaired under dual stresses of heat and orthostatic changes in healthy aged individuals, even if the levels of the stresses are mild.

Optical Resolution of Rimantadine.

This work discloses a new procedure for the resolution of commercially available racemic rimantadine hydrochloride to enantiomerically pure (S)-rimantadine using (R)-phenoxypropionic acid as a recyclable resolving reagent. Good chemical yields, operational ease, and low-cost structure underscore the preparative value of this method for the production of enantiomerically pure rimantadine for medicinal or synthetic studies.

Preparative Method for Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid.

Enantiomerically pure derivatives of 2-amino-4,4,4-trifluorobutanoic acid are in great demand as bioisostere of leucine moiety in the drug design. Here, we disclose a method specifically developed for large-scale (>150 g) preparation of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid. The method employs a recyclable chiral auxiliary to form the corresponding Ni(II) complex with glycine Schiff base, which is alkylated with CF3-CH2-I under basic conditions. The resultant alkylated Ni(II) complex is disassembled to reclaim the chiral auxiliary and 2-amino-4,4,4-trifluorobutanoic acid, which is in situ converted to the N-Fmoc derivative. The whole procedure was reproduced several times for consecutive preparation of over 300 g of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid.